ddn Cancer Research Portal Exclusive: Tackling cancer one genome at a time

PCGP enters second year, sees continued success

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MEMPHIS, Tenn.—Some partnerships can lose their momentumas time goes on, but for the St. Jude Children's Research Hospital – WashingtonUniversity Pediatric Cancer Genome Project (PCGP), that particular problem isnowhere in sight. Four months into its second year, the initiative has alreadyreleased four sets of findings, with more to come.
The initiative began in January 2010. St. Jude is the firstand only National Cancer Institute-designated Comprehensive Cancer Center thatis focused solely on children, and has more than 50 years of experience as wellas an extensive library of tissue samples and data. Washington UniversitySchool of Medicine in St. Louis is a leading genome sequencing center andparticipated in the mapping of the human genome. The project is slated to runthree years, a $65 million undertaking that will sequence and study the cancergenomes of more than 600 children. At the time of the PCGP's origin, a completepediatric cancer genome had yet to be sequenced.
Washington University has received normal and canceroustissue samples from 600 patients from St. Jude's, whose repository houses morethan 50,000 samples. The project is focusing on the most common and mostaggressive pediatric cancers, including brain, blood, bone and other cancers.The data gathered throughout the project began to be reported throughpeer-reviewed channels this year, in addition to being made available throughthe project's Explore website, which offers details on the project's progressas well as additional information on the data gathered so far.
Pediatric cancers remain the leading cause of death bydisease in children over the age of one, and recent studies have found thatwhile childhood cancers can appear in the same organs and locations as adultcancers and share some similarities, they usually have several significantbiological differences.
Dr. Suzanne Baker, corresponding author of the study of oneof the PCGP's recent studies, says she believes the project's focus onpediatric cancers as being different from adult cancers is important. Baker isa member of St. Jude's Department of Developmental Neurobiology and co-leaderof the St. Jude Neurobiology and Brain Tumor Program.
"Pediatric cancers are different from adult cancers in anumber of different ways. Although they're much less common than the mostcommon adult cancers, they are often very selectively seen just in children.And so that suggests that maybe the mutations that drive those tumors inchildren would be different from the ones that are driving cancer in adults,"says Baker. "And so the Pediatric Cancer Genome Project is very important inthe sense that if we didn't take an unbiased look and just try to look at allof the genes across the entire genome and try to identify the mutations thatare frequent in childhood cancer, we might not find those mutations if we werejust looking for things that had already been identified in adult diseases."
The year has been a busy and productive one for the PCGP sofar. In January, the project announced a trio of findings, includingidentifying a new gene target for treating the childhood eye tumorretinoblastoma. Researchers also announced the discovery of a potentialapproach for treating a subtype of acute lymphoblastic leukemia (ALL) known asearly T-cell precursor ALL. On January 29, the PCGP released findings that agenetic mutation had been tied to diffuse intrinsic pontine glioma tumors,which comprise 10 to 15 percent of brain and central nervous system tumors inchildren. (See 'Kids on the brain' for the full story.) Mostrecently, the project discovered the first gene mutation associated with a formof neuroblastoma that affects adolescents and young adults, an alteration thatoffers a clue about the genetic basis of the connection between age atdiagnosis and treatment outcome. That latest discovery was published in theMarch 14 edition of the Journal of the American Medical Association.
According to Baker, there are a variety of cancer types onthe docket to be analyzed, including neuroblastoma, medulloblastoma, severalsubtypes of leukemia and a number of solid tumors.
"I do think because the childhood tumors are less common andtherefore less intensely studied in general, that there may be more unexpectedor novel findings coming out of specifically looking at childhood cancers,"says Baker.
Four months into the project's second year, 265 patients'genomes have been sequenced and analyzed, with 16 of those having beenpublished, according to the PCGP's Explore website. Sequencing is currentlyunderway for 35 more cancerous and regular genomes, with 300 more waiting inthe pipeline.

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